This invention relates to the field of porous foams and methods of preparing these materials. In particular it relates to the art of making porous foams (that are preferably continuous and open celled) from absorbable polymers for biomedical applications using lyophilization.
There is a growing demand for foams for biomedical applications such as buttress materials (U.S. Pat. No. 5,752,965; U.S. Pat. No. 5,263,629; EPA 594 148 A1); scaffolds for tissue engineering (U.S. Pat. No. 5,607,474; WO 94/25079); wound healing dressing; 3D devices such as porous grafts; and other implantable wound healing, augmentation, and regeneration devices (U.S. Pat. No. 5,677,355) etc. Specifically these foams have been made from biocompatible polymers and have had a uniform and open celled microstructure.
Open cell porous biocompatible foams have been recognized to have significant potential for use in the repair and regeneration of tissue. Early efforts in tissue repair focused on the use of biocompatible foam as porous plugs to fill voids in bone. Brekke, et al. (U.S. Pat. No. 4,186,448) described the use of porous mesh work of plugs composed of polyhydroxy acid polymers such as polylactide for healing bone voids. Several attempts have been made in the recent past to make tissue engineering scaffolds using different methods, for example U.S. Pat. No. 5,522,895 (Mikos) and U.S. Pat. No. 5,514,378 (Mikos, et al) using leachables; U.S. Pat. No. 5,755,792 (Brekke) and U.S. Pat. No. 5,133,755 (Brekke) using vacuum foaming techniques; U.S. Pat. No. 5,716,413 (Walter, et al) and U.S. Pat. No. 5,607,474 (Athanasiou, et al) using precipitated polymer gel masses; U.S. Pat. No. 5,686,091 (Leong, et al) and U.S. Pat. No. 5,677,355 (Shalaby, et al) using polymer melt with a fugitive compound that sublimes at temperatures greater than room temperature; and U.S. Pat. No. 5,770,193 (Vacanti, et al) and U.S. Pat. No. 5,769,899 (Schwartz, et al) using textile-based fibrous scaffolds. Hinsch et al (EPA 274,898) described a porous open cell foam of polyhydroxy acids with pore sizes from about 10 to about 200 microns for the in-growth of blood vessels and cells. The foam described by Hincsh could also be reinforced with fibers, yarns braids, knitted fabrics, scrims and the like. Hincsh""s work also described the use of a variety of polyhydroxy acid polymers and copolymers such as poly-L-lactide, poly-DL-lactide, polyglycolide, and polydioxanone. The Hincsh foams had the advantage of having regular pore sizes and shapes that could be controlled by the processing conditions, solvent selected and additives.
Lyophilization lends itself to many advantages when processing thermally sensitive polymers. Further, it lends itself to aseptic processing methodologies for biomedical applications especially when using combinations of polymers with drugs or other bio-active agents such as growth factors, proteins etc. The chief drawback of this process in prior art is that it is the most time consuming and expensive step in the manufacturing operations. It has been realized for some time now that reducing the cycle time will provide significant cost benefits and make this process an even more attractive manufacturing method especially for absorbable polymers, proteins and combinations of these materials incorporating drugs, fillers, excipients, etc. There have been some instances, where this process has been used to make foams from absorbable polymers, but the process of lyophilization in making these foams is far from optimum (U.S. Pat. No. 5,468,253; EPA 274 898 A2; EPA 594 148 A1); often taking more than 3 days to process one batch.
It is therefore, an object of this invention to provide a faster and more economical lyophilization process to make foams for medical foams.
It is a further object of the present invention to provide a lyophilization process for providing foams that are particularly well suited for tissue engineering.
We have discovered a process for making biomedical absorbable foams comprising solidifying a solution of a solvent and a bioabsorbable polymer to form a solid then at a temperature above the apparent Tg of the solid, but below the freezing temperature of the solution, then subliming the solvent out of the solid to provide a biocompatible porous foam.
We have also discovered a process for making biomedical foams with channels therein, comprising solidifying a mixture of a solvent and a bioabsorbable polymer to form a substantially solidified but not completely solidified material, then subliming the solvent out of the material to provide a biocompatible porous foam that has channels.
We have also discovered a process for making biomedical foams with a gradient of pore size therein comprising solidifying a mixture of a solvent and a bioabsorbable polymer to form a substantially solidified but not completely solidified material, then subliming the solvent out of the material to provide a biocompatible porous foam that has a gradient of pores.
These and other objects and advantages of the present invention will be apparent to those skilled in the art from the following Figures, Detailed Description, and Examples.